The objective is to continue investigating the mechanism by which suppressor cells maintain immunologic self-tolerance and regulate the autoimmune response, employing experimental allergic encephalomyelitis (EAE) as a relevant model system. Previously we have shown that Lewis rats rendered tolerant to myelin basic protein (BP) develop suppressor cells that inhibit EAE when transferred to syngeneic recipients. We will now prepare soluble extracts from antigen-specific suppressor lymphocyte populations of tolerant donor rats, and will determine whether these soluble factors will suppress EAE and cellular immunity to BP in syngeneic recipient. Subsequently we will characterize the suppressor factor and determine how it functions with respect to the immunoregulation of EAE. We will also confirm and extend our recent finding that suppressor cell development correlates with recovery from clinical EAE. This may have a direct bearing on our understanding of the pathogenesis of multiple sclerosis, which is characterized by repeated exacerbations and remissions that may reflect changes in immune effector cell and suppressor cell equilibrium in the patient. Studies will be initiated to determine whether antigen blockade or clonal inactivation are also involved in unresponsiveness to EAE.